Response to interferon alfa is hepatitis B virus genotype dependent:: genotype A is more sensitive to interferon than genotype D

被引:195
作者
Erhardt, A [1 ]
Blondin, D [1 ]
Hauck, K [1 ]
Sagir, A [1 ]
Kohnle, T [1 ]
Heintges, T [1 ]
Häussinger, D [1 ]
机构
[1] Univ Dusseldorf, Klin Gastroenterol Hepatol & Infektiol, D-40225 Dusseldorf, Germany
关键词
D O I
10.1136/gut.2004.060327
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background an aims: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated. Patients and methods: HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases. Results: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p < 0.005). Sustained response to IFN was 46% versus 24% (p < 0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p < 0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2xupper limit of normal) as independent positive predictive parameters of IFN response. Conclusions: The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.
引用
收藏
页码:1009 / 1013
页数:5
相关论文
共 35 条
[1]   Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America [J].
Arauz-Ruiz, P ;
Norder, H ;
Robertson, BH ;
Magnius, LO .
JOURNAL OF GENERAL VIROLOGY, 2002, 83 :2059-2073
[2]   Hepatitis B virus genotypes: comparison of genotyping methods [J].
Bartholomeusz, A ;
Schaefer, S .
REVIEWS IN MEDICAL VIROLOGY, 2004, 14 (01) :3-16
[3]   HEPATITIS-B VIRUS UNABLE TO SECRETE E-ANTIGEN AND RESPONSE TO INTERFERON IN CHRONIC HEPATITIS-B [J].
BRUNETTO, MR ;
GIARIN, M ;
SARACCO, G ;
OLIVERI, F ;
CALVO, P ;
CAPRA, G ;
RANDONE, A ;
ABATE, ML ;
MANZINI, P ;
CAPALBO, M ;
PIANTINO, P ;
VERME, G ;
BONINO, F .
GASTROENTEROLOGY, 1993, 105 (03) :845-850
[4]  
BRUNETTO MR, 1995, J HEPATOL, V22, P42
[5]  
DESMET VJ, 1994, HEPATOLOGY, V19, P1513, DOI 10.1002/hep.1840190629
[6]   Lamivudine as initial treatment for chronic hepatitis B in the United States [J].
Dienstag, JL ;
Schiff, ER ;
Wright, TL ;
Perrillo, RP ;
Hann, HWL ;
Goodman, Z ;
Crowther, L ;
Condreay, LD ;
Woessner, M ;
Rubin, M ;
Brown, NA .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (17) :1256-1263
[7]  
*EASL JUR, 2003, J HEPATOL, V38, P533
[8]   Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B [J].
Erhardt, A ;
Reineke, U ;
Blondin, D ;
Gerlich, WH ;
Adams, O ;
Heintges, T ;
Niederau, C ;
Haussinger, D .
HEPATOLOGY, 2000, 31 (03) :716-725
[9]   Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. [J].
Fried, MW ;
Shiffman, ML ;
Reddy, KR ;
Smith, C ;
Marinos, G ;
Goncales, FL ;
Haussinger, D ;
Diago, M ;
Carosi, G ;
Dhumeaux, D ;
Craxi, A ;
Lin, A ;
Hoffman, J ;
Yu, J .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (13) :975-982
[10]   Mechanisms of disease: Hepatitis B virus infection - Natural history and clinical consequences [J].
Ganem, D ;
Prince, AM .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (11) :1118-1129